title: Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta.
abstract: After intraarticular injection of TGF-beta 1 or TGF-beta 2, marked swelling and erythema of the injected joints were apparent within 12-24 h. On a scale of 0 to 4, by day 3, the TGF-beta-treated joints had articular indices (AI) of 3.6 +/- 0.5 to 4.0 +/- 0.0 compared with no response for the vehicle-injected contralateral joints. Histopathologic evaluation revealed a predominantly mononuclear phagocyte infiltrate with some neutrophils and T lymphocytes, consistent with active inflammation. The monocytic pattern of leukocyte infiltration at 2-3 d was comparable to that seen in animals with antigen-induced arthritis after 2-3 wk. Extensive synovial fibroblast hyperplasia became apparent within 48 h, likely as a result of TGF-beta induction of growth factor synthesis by the accumulating monocytes. TGF-beta 2, a homologue of TGF-beta 1, was found to induce a similar level of synovitis and synovial hyperplasia consistent with its parallel monocyte and fibroblast chemotactic properties and ability to induce transcription and translation of monocyte/macrophage-derived growth factors. These data suggest that TGF-beta, released by platelets and activated inflammatory cells, may play a direct role in leukocyte recruitment and activation in arthritic and other chronic inflammatory lesions.
authors.affiliation: Cellular Immunology Section, National Institute of Dental Research, Bethesda, Maryland 20892.
authors.forename: J B
authors.initials: JB
authors.lastname: Allen
authors.forename: C L
authors.initials: CL
authors.lastname: Manthey
authors.forename: A R
authors.initials: AR
authors.lastname: Hand
authors.forename: K
authors.initials: K
authors.lastname: Ohura
authors.forename: L
authors.initials: L
authors.lastname: Ellingsworth
authors.forename: S M
authors.initials: SM
authors.lastname: Wahl
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006965:Hyperplasia; D007249:Inflammation; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008854:Microscopy, Electron; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000633:toxicity; D012016:Reference Values; D013583:Synovial Membrane / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D015291:Transforming Growth Factors / Q000633:toxicity*
chemical_list: D011994:Recombinant Proteins; D015291:Transforming Growth Factors